U.S. patent number 4,971,788 [Application Number 07/303,479] was granted by the patent office on 1990-11-20 for oral cavity and dental microemulsion products.
This patent grant is currently assigned to MediControl Corporation. Invention is credited to Arthur A. Siciliano, Esmail Tabibi.
United States Patent |
4,971,788 |
Tabibi , et al. |
November 20, 1990 |
Oral cavity and dental microemulsion products
Abstract
Oral cavity and dental products are prepared by microemulsifying
an adsorptive oil in an aqueous mediun to produce uniform submicron
sized droplets. The products avoid the generally unaesthetic, oily,
and unpleasant taste problems of previous similar products.
Inventors: |
Tabibi; Esmail (Chelmsford,
MA), Siciliano; Arthur A. (Framingham, MA) |
Assignee: |
MediControl Corporation
(Newton, MA)
|
Family
ID: |
23172302 |
Appl.
No.: |
07/303,479 |
Filed: |
January 27, 1989 |
Current U.S.
Class: |
424/49; 514/943;
514/938 |
Current CPC
Class: |
A61K
8/922 (20130101); A61Q 11/00 (20130101); B82Y
5/00 (20130101); A61K 8/4926 (20130101); A61K
8/06 (20130101); A61K 8/39 (20130101); Y10S
514/943 (20130101); A61K 2800/21 (20130101); Y10S
514/938 (20130101) |
Current International
Class: |
A61K
8/39 (20060101); A61K 8/49 (20060101); A61K
8/92 (20060101); A61K 8/06 (20060101); A61K
8/04 (20060101); A61K 8/30 (20060101); A61Q
11/00 (20060101); A61K 007/16 (); A61K
009/10 () |
Field of
Search: |
;424/49
;514/938,943 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Herzog et al, C.A. 83: 84883g (1975) of Ger. Offen. 2,355,010, May
7, 1975. .
Bilton, C.A. 101: 137044r (1984) of PCT WO 84 02,271, Jun. 21,
1984..
|
Primary Examiner: Rose; Shep K.
Attorney, Agent or Firm: Jacobs; Bruce F.
Claims
What is claimed is:
1. An improved dental and oral hygiene product adapted to remove
odorous compounds, odor-causing bacteria, and other oral disease
causing microbes from an oral cavity and teeth when placed in
contact with the product, wherein the product comprises a stable
uniform submicron emulsion of an adsorptive oil in an aqueous
medium.
2. The product of claim 1 wherein the adsorptive oil is selected
from the group consisting of vegetable oils, mineral oils, fish
oils, animal oils, semi-synthetic and synthetic analogs of said
oils, and mixtures thereof.
3. The product of claim 2 wherein the adsorptive oil is selected
from the group consisting essentially of corn oil, olive oil,
coconut oil, soya bean oil, safflower oil, decane, dodecane,
tetradecane, hexadecane, white mineral oil, and mixtures
thereof.
4. The product of claim 1 wherein the adsorptive oil is in the form
of particles having an average mean diameter less than about 0.5
microns with a size distribution of +/-60%.
5. The product of claim 1 wherein the adsorptive oil is in the form
of particles having an average mean diameter less than about 0.3
microns with a size distribution of +/-50%.
Description
BACKGROUND OF THE INVENTION
This invention relates generally to the preparation composition of
oral cavity and dental products. More specifically, it relates to
products intended to remove bacteria and other microbes from teeth
surfaces and the oral cavity to thereby reduce malodor and
ameliorate other microbial induced disease states.
Oral cavity malodor ("halitosis" or "bad breath") is caused not
only by the odors of food previously eaten but also by the actions
of various microorganisms on the ingested material which produce
odorous sulfur-containing chemicals. The traditional products
currently available for treating oral cavity malodor typically
contain fragrant aromatic flavor oils to mask the malodor. In
addition, they often contain one or more alcohols, abrasives,
antimicrobial agents, and detergents which are believed to inhibit
action of the microorganisms on ingested material by enhancing the
removal of such material from tooth surfaces or by exerting a
microbicidal or static effect. These products conventionally have
the form of mouthwashes, sprays, gels, pastes and the like.
Furthermore, similar compositions have been utilized to inhibit
other oral cavity microorganisms which can cause conditions such as
dental cavities, plaque formation, gingivitis, and the like.
Heretofore, these compositions have been generally
aqueous/alcoholic solutions containing small amounts of aromatic
flavor oils dissolved therein along with one or more alcohols,
abrasives, antimicrobial agents, and detergents. These products
have also been formed as semisolid products by incorporating
conventional water-soluble gelling agents.
Tooth pastes have traditionally been solid dispersions of
abrasives, flavors, detergents, antimicrobial agents, fluorides,
sweeteners and the like.
These products have specific limitations which restrict their use.
For instance, the alcohols can be irritating to portions of the
oral cavity, particularly to abraded areas. Other products
containing high levels of detergents can cause adverse effects such
as gum recession, edema, local irritations, and even allergic
reactions. Moreover, the malodor and microbial suppression is
generally found to remain for a quite short period of time.
One attempt at overcoming some of these problems is disclosed in
U.S. Pat. No. 4,525,342 which teaches the effectiveness of certain
hydrocarbon and fixed vegetable oils in desorbing and binding oral
cavity microbes which cause malodor and disease. The compositions
comprise two phases, one an oily phase and the other an aqueous
phase, which are mixed just prior to use, generally by swishing in
the mouth. Such a product suffers from the disadvantage of being
unaesthetic, oily, and unpleasant to the taste. In addition, it
requires a special dispenser to accurately meter the correct
proportion of each phase into the mouth on a consistent basis. The
crude emulsion formed by swishing in the mouth of the user in the
absence of emulsifiers will inherently consist of very large oil
droplets, typically in the 10 to 100 micron range. Also since
people vary significantly in their swishing action, there will be a
significant variation in effectiveness of the product.
Accordingly, it is an object of the present invention to produce
fluid, gel, or paste emulsions having essentially uniform submicron
size to be used in the oral cavity to reduce malodor and to
ameliorate microbe-mediated diseases.
It is a further object to produce such products having enhanced
effectiveness, reduced irritation potential, sustained duration of
action, extended shelf life, pleasant taste and appearance
characteristics.
These and other advantages will be apparent from the detailed
description of the invention below.
SUMMARY OF THE INVENTION
It has been discovered that oral cavity and dental products
comprised of uniform submicron adsorptive oil particles uniformly
distributed in an aqueous phase produce improved removal of odorous
compounds, odor-causing bacteria, and disease-causing microbes. The
products of this invention are prepared by subjecting a mixture of
at least an adsorptive oil, water, and an emulsifier to ultra high
energy mixing, i.e. Microfluidizer.RTM. processing. Optionally,
other water- soluble, oil-soluble, or amphiphilic materials may
also be present.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The oral cavity and dental products of the present invention are
uniform submicron adsorptive oil particles uniformly dispersed in
an aqueous phase.
The adsorptive oils suitable for use herein include physiologically
acceptable hydrocarbons, vegetable oils, mineral oils, fish oils,
animal oils, semi-synthetic and synthetic analogs thereof, and
mixtures thereof. The adsorptive oils have been shown to be
effective for the removal of the unpleasant odor from saliva
samples which have been allowed to putrify. Preferably the
adsorptive oil is selected from corn oil, olive oil, coconut oil,
soya bean oil, safflower oil, decane, dodecane, tetradecane,
hexadecane, white mineral oil, and mixtures thereof.
Emulsifiers suitable for use herein to form the emulsified oils
include the conventional physiologically acceptable emulsifiers
generally recognized as safe for human consumption. Examples of
suitable emulsifiers include those of the general classes of
anionic, cationic, and nonionic emulsifiers appropriate for use in
the oral cavity or generally recognized as safe in 21 CFR 170-1999
and other parts of the CFR. Specific examples of suitable
emulsifiers include lecithin, saponins, sodium lauryl sulfate,
sodium lauryl sarcosinate, cetyl pyridinium chloride, glyceryl
esters, sorbitan esters, polyoxyethylene sugar esters, block
copolymers of propylene/ethylene oxide, and the like. The
emulsifiers may be used singly or in mixtures. Generally the total
emulsifier content will be on the order of about 0.01 to about 10.0
percent by weight based on the weight of the product. Preferable
amounts of emulsifier will be about 0.05 to about 5.0 weight
percent. Most preferably the amounts will be about 0.1 to about 2.0
weight percent.
In addition to the adsorptive oil and emulsifier, the present oral
cavity and dental products may contain one or more water-soluble,
oil-soluble, or amphiphilic materials which are conventionally
incorporated in such products. For instance, the products may
contain antimicrobials, antifungals, fluorides, preservatives,
sweeteners, flavors, chelating agents, colors, stabilizers,
thickeners, abrasives, bulking agents, emollients, aromatics,
desensitizers, antioxidants, and the like. These materials, when
present, are used in their conventional amounts, i.e. up to about
50 weight percent of the total composition, though generally in
much lower amounts.
To commence the preparation of the uniform submicron adsorptive oil
particles uniformly dispersed in an aqueous phase, the basic oil
phase is first prepared. Thus, any oil-soluble components in the
desired product are mixed together with the adsorptive oil to form
an oil phase. The aqueous phase optionally containing any
water-soluble components (generally other than the thickeners
and/or bulking agents) is prepared by dissolving in at least a
minor portion of the total water to be used to form an aqueous
phase. Alternatively, the other water-soluble components may be
added to the uniform submicron emulsion produced herein. Any
amphiphilic materials to be included may be added to either the oil
or aqueous phase though generally they will be included in the
aqueous phase as this has been found to make formation of the
emulsified adsorptive oil particles more efficient. Thereafter, the
aqueous phase is generally added to the oil phase (though reverse
addition could also be used) with conventional mixing, e.g. a
propellar mixer, to form a crude emulsion similar to what would be
formed in a person's mouth by swishing. Any water not included in
the preliminary aqueous phase above is then added to dilute the
composition to the desired concentration.
To convert the crude initial emulsion above to the uniform
submicron emulsion of the present invention the crude emulsion is
subjected to an ultra high energy mixing device, i.e. a
Microfluidizer which can generally form microemulsions showing
limited stability in the absence of an emulsifier. A particularly
suitable such device is available from Microfluidics Corporation,
Newton, Mass., and is described in U.S. Pat. No. 4,533,254, the
subject matter of which is hereby incorporated by reference. The
ultra high energy mixing device serves to convert the crude
oil-in-water emulsion to a uniform emulsion containing submicron
sized oil-phase particles without requiring further size alteration
or separation. Typical process conditions for the
Microfluidizer.RTM. process equipment include operating pressures
of about 2,000 to about 20,000 psi and at least one cycle/pass
through the equipment. External process temperatures may be varied
from just above the freezing point of the crude emulsion to just
below its boiling point, preferably in the range of about 4.degree.
C. to about 50.degree. C.
Upon passing the crude emulsion through the device, the result is a
uniform oil-in-water emulsion wherein the oil phase particles have
a submicron particle size (as determined by conventional quasi
elastic laser light scattering particle size determination
instruments) and a narrow size distribution. While a single pass
through the Microfluidizer.RTM. process equipment will form a
relatively uniform composition, it has been found to be more
advantageous to use multiple passes to further decrease the size of
the oil phase particles and to increase the uniformity of the
resultant oral cavity and dental emulsion products. Accordingly, it
is preferable to subject the crude emulsion to about 2 to about 5
passes, though 2 to about 4 passes will produce sufficient
uniformity for most applications.
The Microfluidizer process equipment allows easy preparation of a
uniform submicron oil-in-water emulsion which enhances the
effectiveness of the oral cavity and dental product as compared to
non-uniform relatively large emulsions. In addition, the equipment
is capable of handling varying flow rates ranging from about
several hundred milliliters per minute in a laboratory scale device
to over 50 gallons per minute in a full production scale
device.
The oil-in-water emulsions produced herein contain submicron sized
oil particles uniformly distributed in the aqueous phase.
Preferably the oil particles have mean effective diameters less
than about 0.5 microns and a size distribution less than +/-60%.
Most preferably, the emulsified oil particles will have mean
effective diameters less than about 0.3 microns and a size
distribution less than +/-50%.
If it is desired to thicken the emulsion to form a more viscous
product, even a gel or a paste, the desired thickener or bulking
agent (along with any water-soluble components not included in the
initial aqueous phase used to prepare the submicron emulsions) may
be slowly added to the submicron emulsion with stirring.
It has been discovered that by using a uniform submicron emulsified
adsorptive oil in place of the crude, non-uniform, large oil
particles, improved products having increased sorption and binding
activity result. Hence, the products of the present invention
exhibit longer levels of higher activity than the previous
ones.
The improved oral cavity and dental products which are prepared
herein include mouthwashes, non-abrasive dentifrice gels, abrasive
toothpastes and the like. As these products have been prepared
before, but not containing the uniform submicron emulsions of the
present invention, further details on them is readily available in
the prior art and is not repeated here. Any conventional additives
useful in these products may also be incorporated in the present
products by dissolving it in either the oil or aqueous phases prior
to the emulsion formation.
The practice of this invention is illustrated by, but not limited
to, the following examples in which all parts and percents are by
weight unless otherwise specified.
EXAMPLE I
Preparation and Evaluation of Mouthwash
To prepare a mouthwash in accordance with this invention, an oil
phase is prepared containing the following ingredients in the
stated percents of the final mouthwash:
______________________________________ Ingredient Percent
______________________________________ Corn oil 10.0 Glyceryl
monooleate 0.3 Octaglyceryl monooleate 0.7 t-Butylhydroquinone
0.001 Spearmint flavor 1.0 Methyl paraben 0.1
______________________________________
An aqueous phase is prepared containing:
______________________________________ Ingredient Percent
______________________________________ Water, deionized 10.0 Sodium
saccharine 0.02 Cetyl pyridinium chloride 0.05
______________________________________
The oil phase is added to the aqueous phase with propellar mixing.
Then additional deionized water (77.25%) is added with continued
mixing to form a crude emulsion containing oil particles ranging in
size from submicron to greater than 75 microns, predominantly in
the range of 10 to 100 microns. This crude emulsion is pressure fed
to a laboratory scale Microfluidizer.RTM. M-110 device
(Microfluidics Corp., Newton, Mass.) set to operate at 12,000 psi
at room temperature (23.degree. C.). After three passes through
this equipment a homogeneous submicron oil-in-water emulsion
resulted. Three passes are used to increase the uniformity and to
reduce the size of the oil particles therein.
To thicken the emulsion methyl cellulose (0.4%) is slowly added
using a propellar mixer.
Analysis of the resulting microemulsion using a quasi elastic laser
light scattering particle size determination instrument (Brookhaven
Instruments, Model BI-90, Brookhaven, N.Y.) shows an average oil
droplet size of 0.17 microns with a size distribution of
+/-39%.
To evaluate the effectiveness of the above prepared mouthwash as
compared to a crude emulsion thickened to the same extent,
polystyrene test surfaces are prepared and bacteria are bound
thereto. The degree of effectiveness is determined by contacting
the test surfaces with the two emulsions. The emulsion of the
present removes a substantially greater percentage of the bound
bacteria than does the crude emulsion.
EXAMPLE II
Preparation of Mouthwash
The procedure of Example I is repeated to produce another mouthwash
containing the following ingredients in the oil phase:
______________________________________ Ingredient Percent
______________________________________ Safflower oil 5.0 Mineral
oil 5.0 Sodium lauryl sulfate 0.16 t-Butylhydroquinone 0.001 Methyl
paraben 0.10 Peppermint flavor 1.0
______________________________________
and the following ingredients in the aqueous phase:
______________________________________ Ingredient Percent
______________________________________ Sodium saccharine 0.02
Glycerine 5.0 Water, deionized 10.0
______________________________________
After combining the two phases as in Example I, the balance of the
deionized water (73.67%) is added and the resulting crude emulsion
processed through the Microfluidizer three times at an operating
pressure of 10,000 psi. The resultant mouthwash contains oil
droplets/particles having an average mean diameter of 0.20 microns
with a size distribution of +/-36%. Comparative testing of the
effectiveness of this emulsion as compared to the crude emulsion
shows a similar level of improvement in removing bacteria as in
Example I.
EXAMPLE III
Preparation of Non-Abrasive Dentifrice Gel
The basic procedure of Example I is repeated to produce a
non-abrasive dentifrice gel. The oil phase consists of:
______________________________________ Ingredient Percent
______________________________________ Corn oil 20.0 Sodium lauryl
sulfate 1.0 t-Butylhydroxyquinone 0.0001 Methyl paraben 0.10
Perppermint flavor 1.0 ______________________________________
and the aqueous phase consists of:
______________________________________ Ingredient Percent
______________________________________ Sorbitol solution 5.0 Sodium
saccharine 0.05 Water 21.85
______________________________________
After combining the two phases as in Example I, the resulting crude
emulsion is processed through the Microfluidizer three times at an
operating pressure of 14,000 psi. The resultant non-abrasive
dentifrice gel contains oil droplets/particles having an average
mean diameter of 0.27 microns with a size distribution of +/-43%.
Thereafter, the balance of the deionized water (50.0%) containing
dissolved therein a cellulose gum (1.5%) is added using an anchor
mixer.
EXAMPLE IV
Preparation of Abrasive Toothpaste
To prepare an abrasive toothpaste, 20 g of ultrafine dicalcium
phosphate is added to 80 g of the dentifrice gel of Example III
using an anchor mixer. The resulting suspensoid emulsion paste is
then passed through a colloid mill to make it more uniform.
COMPARATIVE EXAMPLE A
The procedure of Example I is repeated in the absence of any
emulsifier, i.e. the two monooleates are omitted. When the oil
phase and the aqueous phase are mixed the result is immediate
separation upon cessation of mixing. When this material is
processed through the Microfluidizer equipment, the result is an
emulsion which separates after standing for several hours. This
shows that the presence of an emulsifier is necessary for the
preparation of the products of this invention even though the
Microfluidizer is capable of preparing a microemulsion showing
limited stability in the absence of any emulsifiers. In addition,
it shows that the presence of the emulsifier during submicron
emulsion formation is not detrimental to the operation of the
Microfluidizer.
* * * * *